EP0037778B1 - Benzodioxanne 1,4 méthoxy-2 propanolamines, leur préparation et leur application en tant que médicaments - Google Patents

Benzodioxanne 1,4 méthoxy-2 propanolamines, leur préparation et leur application en tant que médicaments Download PDF

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Publication number
EP0037778B1
EP0037778B1 EP81400529A EP81400529A EP0037778B1 EP 0037778 B1 EP0037778 B1 EP 0037778B1 EP 81400529 A EP81400529 A EP 81400529A EP 81400529 A EP81400529 A EP 81400529A EP 0037778 B1 EP0037778 B1 EP 0037778B1
Authority
EP
European Patent Office
Prior art keywords
methoxy
general formula
dioxan
propan
tert
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
EP81400529A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP0037778A1 (fr
Inventor
Gilbert Dr. Chim. Mouzin
Henri Dr. Chim. Cousse
Pol Vilain
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pierre Fabre SA
Original Assignee
Pierre Fabre SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pierre Fabre SA filed Critical Pierre Fabre SA
Priority to AT81400529T priority Critical patent/ATE5722T1/de
Publication of EP0037778A1 publication Critical patent/EP0037778A1/fr
Application granted granted Critical
Publication of EP0037778B1 publication Critical patent/EP0037778B1/fr
Expired legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
    • C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
    • C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D319/20—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to the hetero ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention carried out at the PIERRE FABRE Research Center, relates to new chemical compounds, their preparation process and their application in therapy, in particular in the treatment of hypertension and arrhythmias of various origins.
  • the invention also relates to pharmaceutical compositions containing these active ingredients.
  • the acids capable of leading to therapeutically acceptable salts of the compounds of formula 1 are for example hydrochloric acid, sulfuric acid, phosphoric acid, succinic acid, oxalic acid, tartaric acid, maleic acid and fumaric acid.
  • lower alkyl radical is understood to mean essentially linear or branched alkyl radicals comprising from 1 to 8 and preferably from 1 to 4 carbon atoms.
  • the new compounds of formula 1 can be prepared according to a process comprising the following two reaction stages:
  • the 2-hydromethyl benzodioxane derivatives of formula II, used as synthesis intermediates, can for example be prepared according to J. AUGSTEIN et al ⁇ J. Med. Chem. 8, 446 (1965).
  • reaction mixture After three hours of stirring at room temperature, the reaction mixture is brought to reflux for 1 hour. It is left overnight at room temperature, then evaporated to dryness. The residual oil is taken up in ethyl ether, washed 3 times with water, then dried over sodium sulfate. The solution obtained is filtered and the solution obtained is treated with 6 g of maleic acid in solution in 200 ml of ethyl ether. We ice and we filter; the crude crystals obtained are recrystallized from an ethyl acetate-isopropyl ether mixture.
  • the new compounds of formula 1 according to the present invention having good anti-hypertensive and anti-arrhythmic pharmacological properties, can thus be used in therapy in particular in the treatment of hypertension and arrhythmias of various origins.
  • the substances were administered intravenously and orally.
  • the LD 50 is calculated according to the method of K ⁇ BERBER G. - Arch. Exptl. Pathol. Pharmacol., 162, 1931, 480.
  • Intravenously the LD 50 is between 30 and 100 mg / kg. By oral route the LD 50 is between 600 and 900 mg / kg.
  • the duration of activity is more than 30 minutes in 80% of cases.
  • Tachycardia is caused in dogs by intramural injection of aconitine into the right atrium near the sinus node.
  • the pace rises in proportions of 80 to 100%. Since the atrioventricular pathways have normal permeability, the ventricles are driven at the same frequency.
  • the muscle training threshold voltage After determining the muscle training threshold voltage, it is subjected to increasingly higher frequencies in successive stages until a maximum frequency is obtained for which the tissue is unable to respond to stimuli.
  • the product is added to the bath. Three electric drives are performed in the next 25 minutes. The experiment then continues for 1 hour after rinsing the tank.
  • the compound of tertiobutylamino-3 [(Benzodioxan-1,4) yl-2 methoxy] -1 propanol-2 maleate has little impact on the cardiovascular system. However, it decreases the force of cardiac contraction and peripheral resistance, thus achieving a set of properties aimed at combating hypertension.
  • the compound of tertiobutylamino-3 [(1,4-benzodioxan) yl-2 methoxy] -1 propanol-2 maleate has no diuretic power.
  • these compounds and more especially the compound of tertiobutylamino-3 [(benzodioxan-1,4) yl-2 methoxy] -1 propanol-2 maleate can be used in therapy in the treatment heart problems and more particularly hypertension.
  • These compounds can be used in the form of pharmaceutical compositions in which the active compound is mixed with pharmaceutically acceptable non-toxic diluents or vehicles facilitating their bioavailability.
  • compositions can be administered parenterally, intravenously, or orally or rectally.
  • administration doses may vary in fairly large proportions depending on the route of administration chosen, as well as the type and severity of the condition to be treated.
  • compositions may for example be in the form of tablets, capsules, suppositories, aqueous or oily solutions, aqueous or oily suspensions, emulsions, dispersible powders or solutions in aqueous or oily suspensions for injection.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Preventing Corrosion Or Incrustation Of Metals (AREA)
  • Lubricants (AREA)
EP81400529A 1980-04-04 1981-04-02 Benzodioxanne 1,4 méthoxy-2 propanolamines, leur préparation et leur application en tant que médicaments Expired EP0037778B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT81400529T ATE5722T1 (de) 1980-04-04 1981-04-02 2-(1,4-benzodioxanyl)-methoxy-propanolamine, verfahren zu deren herstellung und verwendung als arzneimittel.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR8007719 1980-04-04
FR8007719A FR2479825A1 (fr) 1980-04-04 1980-04-04 Benzodioxanne 1,4 methoxy-2 propanolamines, leur preparation et leur application en tant que medicaments

Publications (2)

Publication Number Publication Date
EP0037778A1 EP0037778A1 (fr) 1981-10-14
EP0037778B1 true EP0037778B1 (fr) 1983-12-28

Family

ID=9240576

Family Applications (1)

Application Number Title Priority Date Filing Date
EP81400529A Expired EP0037778B1 (fr) 1980-04-04 1981-04-02 Benzodioxanne 1,4 méthoxy-2 propanolamines, leur préparation et leur application en tant que médicaments

Country Status (11)

Country Link
US (2) US4456614A (da)
EP (1) EP0037778B1 (da)
JP (1) JPS56156275A (da)
AT (1) ATE5722T1 (da)
AU (1) AU543364B2 (da)
CA (1) CA1167047A (da)
DE (1) DE3161750D1 (da)
DK (1) DK152288C (da)
ES (1) ES500822A0 (da)
FR (1) FR2479825A1 (da)
ZA (1) ZA812263B (da)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2479825A1 (fr) * 1980-04-04 1981-10-09 Fabre Sa Pierre Benzodioxanne 1,4 methoxy-2 propanolamines, leur preparation et leur application en tant que medicaments
CA1220059A (en) * 1983-10-03 1987-04-07 Edmund Isakov Two-prong rotary bit, especially for use with roof drills, and insert therefor
EP0939135A1 (en) * 1992-12-21 1999-09-01 Duphar International Research B.V Substantially pure hetero-bicyclic alcohol enantiomers
TW200612905A (en) * 2004-06-16 2006-05-01 Janssen Pharmaceutica Nv Novel sulfamate and sulfamide derivatives useful for the treatment of epilepsy and related disorders
MY147767A (en) * 2004-06-16 2013-01-31 Janssen Pharmaceutica Nv Novel sulfamate and sulfamide derivatives useful for the treatment of epilepsy and related disorders
ATE400565T1 (de) * 2004-08-24 2008-07-15 Janssen Pharmaceutica Nv Als antikonvulsive mittel geeignete neue benzokondensierte heteroarylsulfamidderivate
AU2006249577A1 (en) * 2005-05-20 2006-11-30 Janssen Pharmaceutica N.V. Process for preparation of sulfamide derivatives
US20070155827A1 (en) * 2005-12-19 2007-07-05 Smith-Swintosky Virginia L Use of benzo-fused heterocycle sulfamide derivatives for the treatment of depression
US20070155823A1 (en) * 2005-12-19 2007-07-05 Smith-Swintosky Virginia L Use of benzo-fused heterocycle sulfamide derivatives as neuroprotective agents
US8691867B2 (en) * 2005-12-19 2014-04-08 Janssen Pharmaceutica Nv Use of benzo-fused heterocycle sulfamide derivatives for the treatment of substance abuse and addiction
US8716231B2 (en) 2005-12-19 2014-05-06 Janssen Pharmaceutica Nv Use of benzo-fused heterocycle sulfamide derivatives for the treatment of pain
US8937096B2 (en) * 2005-12-19 2015-01-20 Janssen Pharmaceutica Nv Use of benzo-fused heterocyle sulfamide derivatives for the treatment of mania and bipolar disorder
US8497298B2 (en) * 2005-12-19 2013-07-30 Janssen Pharmaceutica Nv Use of benzo-fused heterocycle sulfamide derivatives for lowering lipids and lowering blood glucose levels
AR058389A1 (es) * 2005-12-19 2008-01-30 Janssen Pharmaceutica Nv Uso de derivados heterociclicos benzo-fusionados de sulfamida para el tratamiento de la obesidad
TW200812573A (en) * 2006-05-19 2008-03-16 Janssen Pharmaceutica Nv Co-therapy for the treatment of epilepsy and related disorders
US20090247617A1 (en) * 2008-03-26 2009-10-01 Abdel-Magid Ahmed F Process for the preparation of benzo-fused heteroaryl sulfamates
US20090247618A1 (en) * 2008-03-26 2009-10-01 Ballentine Scott A Process for preparation of benzo-fused heteroaryl derivatives
BRPI0915890A2 (pt) * 2008-06-23 2015-11-03 Janssen Pharmaceutica Nv forma cristalina de (2s)-(-)-n-(6-cloro-2,3-di-hidro-benzo[1,4]dioxin-2-ilmetil)-sulfamida
US8815939B2 (en) * 2008-07-22 2014-08-26 Janssen Pharmaceutica Nv Substituted sulfamide derivatives

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1054104A (da) * 1962-07-20
GB1096301A (en) * 1963-06-20 1967-12-29 Ward Blenkinsop & Co Ltd 1,4-benzodioxane derivatives
GB1058822A (en) * 1963-07-30 1967-02-15 Ici Ltd 3-amino-2-hydroxypropoxy heterocyclic derivatives
GB1521471A (en) * 1974-06-05 1978-08-16 Randall & Son Ltd J Token-deposit locks
FR2358142A1 (fr) * 1976-07-12 1978-02-10 Parcor Nouveaux derives du benzodioxanne
JPS5377081A (en) * 1976-12-20 1978-07-08 Yoshitomi Pharmaceut Ind Ltd 1,4-benzodioxepin derivative, its acid addition salt, and its preparation
US4187313A (en) * 1978-01-30 1980-02-05 Ciba-Geigy Corporation 2-Aminoethyl-1,4-benzodioxans
US4261907A (en) * 1978-01-30 1981-04-14 Ciba-Geigy Corporation Stereospecific process
FR2479825A1 (fr) * 1980-04-04 1981-10-09 Fabre Sa Pierre Benzodioxanne 1,4 methoxy-2 propanolamines, leur preparation et leur application en tant que medicaments

Also Published As

Publication number Publication date
ATE5722T1 (de) 1984-01-15
EP0037778A1 (fr) 1981-10-14
US4456614A (en) 1984-06-26
JPS56156275A (en) 1981-12-02
AU543364B2 (en) 1985-04-18
DK152288C (da) 1988-07-11
US4539413A (en) 1985-09-03
ZA812263B (en) 1982-04-28
DK152288B (da) 1988-02-15
CA1167047A (fr) 1984-05-08
DE3161750D1 (en) 1984-02-02
ES8201572A1 (es) 1982-01-01
JPS649994B2 (da) 1989-02-21
ES500822A0 (es) 1982-01-01
FR2479825A1 (fr) 1981-10-09
FR2479825B1 (da) 1983-07-08
DK153581A (da) 1981-10-05
AU6909981A (en) 1981-10-08

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